Anxiety is one of the most common mental disorders worldwide. Currently, the main anti-anxiety drugs, selective serotonin/noradrenalin reuptake inhibitors (SSRIs/SNRIs), are always associated with delayed onset of action and low therapeutic response rate. Benzodiazepines can produce rapid effects, but their long-term use may result in severe adverse reaction and drug dependence. Transcranial direct current stimulation (tDCS) is one of the noteworthy noninvasive brain stimulation techniques and is expected to be a new choice of anti-anxiety therapy. However, the underlying mechanism remains unclear. In our recent published study, we have observed the important role of endogenous cannabinoid in the pathophysiology and treatment of anxiety. Here we verified the anti-anxiety effects of tDCS in the acute stress exposure rats, and investigated the possible role of amygdala cannabinoid receptor 1 (CB1R) activation in the anti-anxiety response of tDCS. Forced swimming exposure produced anxiety-like behaviors, which can be reversed by tDCS treatment. tDCS increased the time spent in the center without affection of locomotor activity in open field test (OFT) and elevated the number of entries into open arm and time spent in open arm in elevated plus maze test (EPMT). However, Inhibition of CB1R function by AM251 intraperitoneal injection or CB1R knockdown in amygdala produced the negative effects on the anti-anxiety action of tDCS. In conclusion, tDCS may play an anti-anxiety role at least partly via activation of amygdala CB1R, which provides a theoretical basis for the clinical application of tDCS in the treatment of anxiety disorder.

焦虑是全球最常见的精神障碍之一。目前，主要的抗焦虑药物，选择性5-羟色胺/去甲肾上腺素再摄取抑制剂（SSRIs/SNRIs），总是与起效延迟和治疗反应率低有关。苯二氮卓类药物起效迅速，但长期使用可能导致严重的不良反应和药物依赖。经颅直流电刺激（tDCS）是一种值得注意的无创脑刺激技术，有望成为抗焦虑治疗的新选择。然而，潜在的机制仍不清楚。在我们最近发表的研究中，我们观察到内源性大麻素在焦虑的病理生理学和治疗中的重要作用。在这里，我们验证了 tDCS 在急性应激暴露大鼠中的抗焦虑作用，并研究了杏仁核大麻素受体 1 (CB1R) 激活在 tDCS 抗焦虑反应中的可能作用。强迫游泳暴露产生焦虑样行为，可以通过 tDCS 治疗逆转。tDCS 在开放场测试 (OFT) 中增加了在中心停留的时间而不影响运动活动，并增加了进入开放臂的次数和在高架十字迷宫测试 (EPMT) 中花费在开放臂的时间。然而，AM251腹腔注射或杏仁核中CB1R敲低对CB1R功能的抑制对tDCS的抗焦虑作用产生负面影响。综上所述，tDCS可能至少部分通过激活杏仁核CB1R发挥抗焦虑作用，这为tDCS在焦虑症治疗中的临床应用提供了理论依据。